Racial differences in treatment adherence and response to acupuncture and cognitive behavioral therapy for insomnia among Black and White cancer survivors

Abstract Background Racial disparities in sleep are well‐documented. However, evidence‐based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT‐I) among Black and White cancer survivors. Methods We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT‐I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co‐morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants. Results Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all p < 0.05). Black survivors demonstrated lower adherence to CBT‐I than White survivors (61.5% vs. 88.5%, p = 0.006), but their treatment response to CBT‐I was similar to white survivors. Black survivors had similar adherence to acupuncture as white survivors (82.3% vs. 93.4%, p = 0.16), but they had greater reduction in insomnia severity with acupuncture (−3.0 points, 95% CI −5.4 to 0.4, p = 0.02). Conclusion This study identified racial differences in sleep characteristics, as well as treatment adherence and responses to CBT‐I and acupuncture. To address racial disparities in sleep health, future research should focus on improving CBT‐I adherence and confirming the effectiveness of acupuncture in Black cancer survivors.


| INTRODUCTION
Insomnia is a prevalent, disruptive, and costly condition that affects up to two-thirds of cancer survivors. 1,24][5][6][7][8] A growing body of research has demonstrated that Black individuals experience shorter, lighter, and more fragmented sleep than their white counterparts. 9Therefore, improving sleep health has been identified as a potential approach to reduce racial disparities in cancer-related outcomes and promote more equitable cancer care. 10,11hile racial disparities in sleep are well-documented, there is a paucity of research on effective interventions to improve sleep health in Black cancer patients. 9,12][15] Acupuncture and cognitive-behavioral therapy for insomnia (CBT-I) are evidence-based, non-pharmacological treatments that have demonstrated effectiveness for insomnia in cancer survivors. 16,17However, due to underrepresentation of Black individuals in these clinical trials, their adherence and responses to these two interventions have not been well-studied.
The aim of the current study is to evaluate racial differences between Black and White cancer survivors with regards to insomnia severity, sleep characteristics, and comorbid symptoms, as well as treatment attitudes, adherence, and responses to acupuncture and CBT-I, using data from a comparative effectiveness trial completed by our group. 18The findings are intended to help inform future research on evidence-based interventions to reduce sleep health disparities in oncology.

| Design, setting, and participants of a comparative effectiveness trial
We conducted the sub-group analysis of a randomized clinical trial that examined the comparative effectiveness of acupuncture versus CBT-I in cancer survivors with insomnia.The parent trial protocol and primary findings have been published previously. 18,19Briefly, the trial was conducted at two academic cancer centers from February 2015 to July 2017.Inclusion criteria were: (1) Englishspeaking adults with a cancer diagnosis of any type or stage; (2) completion of cancer treatment with surgery, chemotherapy, and/or radiotherapy at least 1 month before enrollment; (3) score ≥8 on the Insomnia Severity Index; 20 and (4) insomnia disorder criteria as defined by the Diagnostic and Statistical Manual of Mental disorders, 5th Edition DSM- (5). 21Exclusion criteria were: (1) other inadequately treated sleep disorders; (2) prior insomnia treatment with acupuncture or CBT-I; (3) inadequately treated psychiatric disorder; and (4) shift work that interferes with establishing regular sleep schedule.Eligible patients completed informed consent and were randomized in a 1:1 ratio to one of the two interventions using permuted block randomization with full allocation concealment.Study investigators were blinded to treatment assignment.The study was approved by the institutional review boards at the University of Pennsylvania and Memorial Sloan Kettering Cancer Center.Through dedicated efforts in patient engagement and outreach, 19,22 the parent trial enrolled a diverse study population with 27% of trial participants identifying as Black, thereby allowing for exploratory sub-group analyses.In the current study, we conducted a secondary analysis restricted to Black and White trial participants.

| Interventions
Acupuncture is a non-pharmacologic modality from Traditional Chinese Medicine (TCM) in which practitioners insert thin, sterile, single-use, metallic needles into the body surface to achieve therapeutic effects. 23In this study, licensed acupuncturists with over 10 years of experience delivered the intervention using a manualized protocol.The protocol included standardized points to address insomnia and supplementary points to treat co-morbid symptoms (e.g., anxiety, pain).Participants received acupuncture treatments twice per week for the first two weeks, followed by weekly for the six remaining weeks, equaling a total of 10 treatments.
CBT-I is a manualized multi-component intervention that includes sleep restriction, stimulus control, cognitive restructuring, relaxation training, and sleep hygiene education. 24Four licensed therapists and five psychology trainees delivered the CBT-I intervention.Patients received five weekly sessions followed by two bi-weekly sessions for a total of seven sessions over 8 weeks.

| Outcomes
Insomnia severity, sleep characteristics, co-morbid symptoms (pain, fatigue, anxiety, depression), and healthrelated quality of life were assessed using validated patient-reported outcomes.The primary outcome of the parent comparative effectiveness trial was insomnia severity as assessed by the Insomnia Severity Index (ISI).Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). 26Sleep onset latency (time to fall asleep), wake after sleep onset (amount of time spent awake during the night), total sleep time, and sleep efficiency (percentage of time in bed actually sleeping) was calculated using the Consensus Sleep Diary (CSD). 27ain severity was assessed using the Brief Pain Inventory (BPI).28 Fatigue was assessed using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF).29 Anxiety and depression was assessed using the Hospital Anxiety and Depression Scale. 30Physical health-and mental health-related quality of life were assessed using the PROMIS-Global Health.31 To assess views and attitudes towards acupuncture and CBT-I, we used the Treatment Acceptability and Preference (TAP) scale.32 A patient advisory panel collaborated with the research team to develop brief descriptions of acupuncture and CBT-I, including intervention components, treatment schedule (i.e., number of sessions, frequency, and mode of delivery), potential benefits and risks, and role of the treatment provider. 19his information was presented to patients at a 6th grade reading level before the TAP scale was administered.The TAP scale asks patients about their views towards four attributes of the interventions: (1) appropriateness (i.e., does the treatment seem logical for addressing insomnia?);( 2) suitability (i.e., does the treatment fit a patient's lifestyle); ( 3) effectiveness (i.e., is this treatment effective for insomnia?); an (4) convenience (i.e., is the patient willing to apply and adhere to the treatment?).Patients rated each attribute on a 5-point scale indicating level of agreement: "not at all" (0), "somewhat" (1), "neutral" (2), "very" (3), and "very much" (4).A total score is calculated as a mean of the four attribute scores to reflect overall treatment acceptability; higher scores indicate that patients perceive the intervention as more appropriate, suitable, effective, and convenient.The TAP scale has demonstrated internal consistency, reliability, and factorial validity. 32e administered the TAP scale at baseline prior to randomization and receipt of the treatments.
We also assessed treatment adherence by tracking the number of sessions attended.Patients were considered adherent to treatments if they attended ≥80% of the treatment sessions.

| Statistical analyses
We used Student's t-tests and chi-squared tests to evaluate racial differences in insomnia severity, sleep characteristics, co-morbid symptoms, TAP scale scores, and treatment adherence.To evaluate the impact of race on treatment response, we developed a multivariable linear regression model, with the total ISI score at Week 8 (end of treatment) as the dependent variable, race as the independent variable (White race as the reference), and baseline ISI score as the covariate.We also repeated the regression model for other sleep outcomes, that is PSQI score and all CSD variables.The regression analyses were performed in each treatment group separately.The sample size was pre-determined by the parent trial. 18All analyses were post-hoc.All statistical tests were two-sided.Statistical significance was set at p < 0.05.All statistical analyses were conducted using STATA (version 15.0; STATA Corporation, College Station, TX).

| RESULTS
Participant characteristics are summarized in Table 1.Among the 160 patients enrolled in the parent trial, 43 were Black and 113 were White.Of these 156 patients, 78 were assigned to receive acupuncture and 78 were assigned to receive CBT-I.
Baseline sleep characteristics and co-morbid symptoms differed by race (Table 2).White survivors experienced insomnia symptoms for a longer duration (10.4 [SD 9.6] vs. Black and White survivors had no significant differences in their views about the appropriateness, suitability, and effectiveness of acupuncture and CBT-I.However, compared with White survivors, Black survivors viewed both interventions as less convenient.Regarding the convenience of acupuncture, 74.4% of Black survivors responded "very" or "very much" to the TAP convenience item (i.e., willing to apply and adhere to the treatment), compared with 90.3% of White survivors (p = 0.03).Regarding the convenience of CBT-I, 57.1% of Black survivors responded "very" or "very much" to the TAP convenience item, compared with 79.6% of white survivors (p = 0.04).
Treatment adherence differed by race.With respect to acupuncture, 82.3% of Black survivors adhered to treatments, compared to 93.4% of White survivors (p = 0.16).With respect to CBT-I, 61.5% of Black survivors adhered to treatments, compared to 88.5% of white survivors (p = 0.006).
In multivariable linear regression analyses of acupuncture recipients, Black race was associated with a greater post-treatment reduction in the ISI score (−3.0, 95% CI

| DISCUSSION
Racial disparities in sleep represent a significant public health concern, 9,33 and growing research has identified sleep as a promising intervention target to reduce racial inequities in cancer and other chronic diseases. 11In this secondary analysis of a comparative effectiveness trial with over 25% of trial participants who identified as Black, we observed racial differences in sleep characteristics, as well as treatment adherence and responses, which could potentially be leveraged to improve sleep interventions for Black cancer populations.
Our study revealed that Black survivors had lower rates of adherence to CBT-I but similar rates of adherence to acupuncture, compared to their white counterparts.[36][37] Given that CBT-I involves techniques that must be applied in everyday settings and home environments, it is possible that some individuals who live in unsafe neighborhoods or poor housing conditions may find it challenging to adhere to CBT-I.By contrast, not only did more Black survivors view acupuncture as convenient, but they also demonstrated higher rates of adherence to acupuncture than to CBT-I.While many acupuncturists counsel patients on lifestyle modification in addition to administering the needling techniques, patients may view acupuncture as primarily a receptive therapy in contrast to CBT-I, which requires more active participation and application of skills by patients.This receptive nature of the intervention may have contributed to perceptions of acupuncture as convenient.However, the underlying reasons for higher acupuncture adherence among Black survivors still requires further exploration in future research.This new understanding could potentially be applied to other sleep interventions to address barriers to adherence.
Despite lower adherence to CBT-I, Black participants experienced similar treatment response to CBT-I relative to their white counterparts.Given that CBT-I is a skillbased intervention, it is possible that participants were able to learn helpful techniques that they could immediately apply in daily life, even if they did not complete all the remaining sessions.These findings suggest that greater focus should be placed on increasing access to CBT-I and removing barriers to initiating treatment among Black patients. 38There are also recent efforts to tailor CBT-I to Of note, acupuncture produced greater reduction in insomnia severity and minutes awake after sleep onset among Black survivors compared with White survivors.Although the reasons for this differential response to acupuncture require further investigation, it is possible that Black patients have a unique insomnia phenotype better suited for acupuncture. 42,43Consistent with other research demonstrating racial disparities in pain and sleep outcomes, 9,12,44,45 the Black survivors in our study reported higher pain severity and poorer physical health-related quality of life, as well as longer sleep onset latency and poorer sleep quality.Pain and sleep disturbances are known to have a bi-directional relationship, 46,47 suggesting that each symptom could potentially exacerbate or perpetuate the other if both are not adequately treated.Research from our group has shown that acupuncture not only can jointly treat pain and sleep disturbances, 48 but also may produce improvements in insomnia by reducing co-morbid pain, 49 which is a prevalent symptom in cancer survivors.As such, acupuncture may represent an optimal treatment approach for Black survivors with co-occurring insomnia and pain, particularly those who are unable to pursue separate treatments for each health issue due to time and financial toxicities or other barriers. 50,51ur findings must be considered in the context of several limitations.We conducted a post-hoc sub-group analysis of a parent comparative effectiveness trial, so the findings are hypothesis-generating rather than confirmatory.Due to limited enrollment of other racial/ethnic groups, this study included only Black and White trial participants.Future studies should examine other racial and ethnic groups to provide a more comprehensive understanding of sleep health disparities.The parent trial was also conducted before the widespread adoption of telehealth during the COVID-19 pandemic.Since CBT-I, unlike acupuncture, can be delivered remotely, perceptions and attitudes towards these two modalities may have changed.Finally, most trial participants were relatively well-educated and receiving care at a tertiary academic cancer center, so the generalizability of our findings may be limited.
Despite these limitations, this study is one of the first to document racial differences in treatment adherence and response to acupuncture and CBT-I among Black and White cancer survivors.Compared to their white counterparts, Black cancer survivors had similar improvements in sleep with CBT-I but experienced greater improvements with acupuncture, suggesting that both are promising tools to address sleep disparities in this population.Future research should build on these findings and focus on improving CBT-I adherence and confirming acupuncture effectiveness among Black cancer survivors.

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Patient characteristics.et al. −5.4 −0.5, p = 0.02) and minutes awake after sleep onset (−20.0,95% CI −36.6 to −3.3, p = 0.02), after adjusting for baseline ISI score and baseline minutes awake after sleep onset, respectively.By contrast, when CBT-I recipients were evaluated in the multivariable linear regression model, race was not significantly associated with any posttreatment sleep outcomes, after adjusting for baseline scores.